The principle aim of this project is to conduct molecular genetic research on alcoholism by collecting 50 multiplex pedigrees, studying linkage to loci that have shown provisional evidence of linkage and candidate gene loci, and to pool cell lines with other centers participating in the collaborative study for systematic genome mapping of disease genes. Pedigrees will be identified on the basis of an alcoholic proband a minimum of 2 additional alcoholic relatives and a minimum of one additional relative with either alcoholism or alcoholism-related disorders (depression or antisocial personality disorder, i.e., depression spectrum disease). The pedigrees will be extended to include an estimated 10-20 subjects per pedigree. Pedigree members will be interviewed, diagnosed by DSM-IIIR aids I and II, any have lymphoblastoid cell lines cultured and cryopreserved. Loci to be studied at Iowa include those showing provisional evidence of linkage to alcoholism or depression spectrum disease(esterase D and orosomucoid, respectively), and' p those that can be consider-ed candidate gene loci (alcohol and aldehyde dehydrogenases). Linkage will by analyzed using two classifications of affected state: alcoholism alone, and alcoholism or depression or antisocial personality disorder (depression spectrum disease). Cell lines will be shared with other collaborating centers for a systematic search for alcoholism disease genes at a laboratory to be decided upon by the collaborators.